PMID- 24928046 OWN - NLM STAT- MEDLINE DCOM- 20140902 LR - 20140614 IS - 1096-0341 (Electronic) IS - 0042-6822 (Linking) VI - 458-459 DP - 2014 Jun TI - Biogenesis of non-structural protein 1 (nsp1) and nsp1-mediated type I interferon modulation in arteriviruses. PG - 136-50 LID - S0042-6822(14)00151-2 [pii] LID - 10.1016/j.virol.2014.04.028 [doi] AB - Type I interferons (IFNs-alpha/beta) play a key role for the antiviral state of host, and the porcine arterivirus; porcine reproductive and respiratory syndrome virus (PRRSV), has been shown to down-regulate the production of IFNs during infection. Non-structural protein (nsp) 1 of PRRSV has been identified as a viral IFN antagonist, and the nsp1alpha subunit of nsp1 has been shown to degrade the CREB-binding protein (CBP) and to inhibit the formation of enhanceosome thus resulting in the suppression of IFN production. The study was expanded to other member viruses in the family Arteriviridae: equine arteritis virus (EAV), murine lactate dehydrogenase-elevating virus (LDV), and simian hemorrhagic fever virus (SHFV). While PRRSV-nsp1 and LDV-nsp1 were auto-cleaved to produce the nsp1alpha and nsp1beta subunits, EAV-nsp1 remained uncleaved. SHFV-nsp1 was initially predicted to be cleaved to generate three subunits (nsp1alpha, nsp1beta, and nsp1gamma), but only two subunits were generated as SHFV-nsp1alphabeta and SHFV-nsp1gamma. The papain-like cysteine protease (PLP) 1alpha motif in nsp1alpha remained inactive for SHFV, and only the PLP1beta motif of nsp1beta was functional to generate SHFV-nsp1gamma subunit. All subunits of arterivirus nsp1 were localized in the both nucleus and cytoplasm, but PRRSV-nsp1beta, LDV-nsp1beta, EAV-nsp1, and SHFV-nsp1gamma were predominantly found in the nucleus. All subunits of arterivirus nsp1 contained the IFN suppressive activity and inhibited both interferon regulatory factor 3 (IRF3) and NF-kappaB mediated IFN promoter activities. Similar to PRRSV-nsp1alpha, CBP degradation was evident in cells expressing LDV-nsp1alpha and SHFV-nsp1gamma, but no such degradation was observed for EAV-nsp1. Regardless of CBP degradation, all subunits of arterivirus nsp1 suppressed the IFN-sensitive response element (ISRE)-promoter activities. Our data show that the nsp1-mediated IFN modulation is a common strategy for all arteriviruses but their mechanism of action may differ from each other. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Han, Mingyuan AU - Han M AD - Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA. FAU - Kim, Chi Yong AU - Kim CY AD - Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA. FAU - Rowland, Raymond R R AU - Rowland RR AD - Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS 66506, USA. FAU - Fang, Ying AU - Fang Y AD - Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS 66506, USA. FAU - Kim, Daewoo AU - Kim D AD - Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA. FAU - Yoo, Dongwan AU - Yoo D AD - Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA. Electronic address: dyoo@illinois.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20140513 PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (Interferon Type I) RN - 0 (Viral Nonstructural Proteins) SB - IM MH - Animals MH - Arteriviridae/genetics/*metabolism MH - Cell Line MH - Cloning, Molecular MH - Gene Expression Regulation, Viral/*physiology MH - Humans MH - Interferon Type I/*metabolism MH - Viral Nonstructural Proteins/genetics/*metabolism MH - Virus Replication OTO - NOTNLM OT - Arteriviridae OT - CBP degradation OT - EAV OT - IFN antagonism OT - LDV OT - PRRSV OT - SHFV OT - nsp1 EDAT- 2014/06/15 06:00 MHDA- 2014/09/03 06:00 CRDT- 2014/06/15 06:00 PHST- 2014/02/07 00:00 [received] PHST- 2014/03/03 00:00 [revised] PHST- 2014/04/22 00:00 [accepted] PHST- 2014/06/15 06:00 [entrez] PHST- 2014/06/15 06:00 [pubmed] PHST- 2014/09/03 06:00 [medline] AID - S0042-6822(14)00151-2 [pii] AID - 10.1016/j.virol.2014.04.028 [doi] PST - ppublish SO - Virology. 2014 Jun;458-459:136-50. doi: 10.1016/j.virol.2014.04.028. Epub 2014 May 13.